Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002046759 | SCV002117420 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 455 of the MUSK protein (p.Tyr455Asp). This variant is present in population databases (rs369240171, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1349071). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002545367 | SCV003590236 | uncertain significance | Inborn genetic diseases | 2021-11-15 | criteria provided, single submitter | clinical testing | The c.1363T>G (p.Y455D) alteration is located in exon 11 (coding exon 11) of the MUSK gene. This alteration results from a T to G substitution at nucleotide position 1363, causing the tyrosine (Y) at amino acid position 455 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |